A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma: results from the CAPRA study

Ann W. Silk, Steven J. O’Day, Howard L. Kaufman, Jennifer Bryan, Jacqueline T. Norrell, Casey Imbergamo, Daniella Portal, Edwin Zambrano-Acosta, Marisa Palmeri, Seymour Fein, Cai Wu, Leslie Guerreiro, Daniel Medina, Praveen K. Bommareddy, Andrew Zloza, Bernard A. Fox, Carmen Ballesteros-Merino, Yixin Ren, Darren Shafren, Mark GroseJoshua A. Vieth, Janice M. Mehnert

Research output: Contribution to journalArticlepeer-review

Abstract

Background: CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB–IV melanoma. Methods: Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety. Results: Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3+ infiltrates. Surprisingly, the baseline cell density of CD3+CD8 T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (P = 0.0179). Conclusions: These findings suggest responses to this combination may be seen even in patients without a typical “immune-active” microenvironment. Trial registration number: NCT02565992.

Original languageEnglish (US)
Pages (from-to)1405-1415
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume72
Issue number6
DOIs
StatePublished - Jun 2023
Externally publishedYes

Keywords

  • Clinical trial
  • Melanoma
  • Oncolytic virus
  • Pembrolizumab
  • V937

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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